title: Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells.
abstract: Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Garth W
authors.initials: GW
authors.lastname: Tormoen
authors.forename: Olivia
authors.initials: O
authors.lastname: Recht
authors.forename: András
authors.initials: A
authors.lastname: Gruber
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.forename: Owen J T
authors.initials: OJ
authors.lastname: McCarty
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001777:Blood Coagulation; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D010718:Phosphatidylserines / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D010718:Phosphatidylserines; D003630:Daunorubicin